Abstract:Epidemiological surveys confirmed that type 2 diabetes mellitus (T2DM) and depression are often comorbid. Evidence from animal and clinical researches showed that hyperactivation of the hypothalamic- pituitary- adrenal (HPA) axis, and changes in genes, neurotransmitters and inflammatory mediators may play the important roles in the comorbidity of these two chronic illnesses. Different anti- depressants have various influences on the control of blood glucose, so appropriate antidepressants or psychosocial and psychological interventions may contribute to the comprehensive management of T2DM patients with comorbid depression. Since diagnosis and treatment of depression require professional expertise, it is psychopathy specialists who ought to evaluate and provide systemic treatment program.